ArticleJournal of hepatology2022
Role of the IgG4-related cholangitis autoantigen annexin A11 in cholangiocyte protection.
Article in Journal of hepatology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- Identification of candidate biomarkers for diagnosis, disease activity, and relapse prediction in IgG4-related disease.Arthritis research & therapy · 2026Article
- Physiological and pathological roles of ANXA11: a multifunctional regulator in neurodegeneration and other disorders.Cell communication and signaling : CCS · 2026Review
- IgG4-related sclerosing cholangitis: navigating diagnostic dilemmas and the challenge of relapse.Frontiers in medicine · 2026Review
- Inflammation and immunity in liver homeostasis and disease: a nexus of hepatocytes, nonparenchymal cells and immune cells.Cellular & molecular immunology · 2025Review
- IgG4-Related Cholangitis.Seminars in liver disease · 2025Review
- Review
- Update on Autoimmune Pancreatitis and IgG4-Related Disease.United European gastroenterology journal · 2025Review
- Management of IgG4-related cholangitis: diagnosis, therapy, and long-term surveillance.Gastroenterology report · 2025Review
- Laminin 511-E8, an autoantigen in IgG4-related cholangitis, contributes to cholangiocyte protection.JHEP reports : innovation in hepatology · 2024Article
- IgG4 autoantibodies and autoantigens in the context of IgG4-autoimmune disease and IgG4-related disease.Frontiers in immunology · 2024Review
- Galectin-3 and prohibitin 1 are autoantigens in IgG4-related cholangitis without clear-cut protective effects against toxic bile acids.Frontiers in immunology · 2023Article
- The spectrum of B cells in the pathogenesis, diagnosis and therapeutic applications of immunoglobulin G4-related disease.Clinical & translational immunology · 2023Review
- Autoantibody formation against a canalicular epitope found in a patient with acute intrahepatic cholestasis with PFIC-like presentation.JHEP reports : innovation in hepatology · 2022Article
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsAnnexin A11 was identified as autoantigen in IgG4-related cholangitis (IRC), a B-cell driven disease. Annexin A11 modulates calcium-dependent exocytosis, a crucial mechanism for insertion of proteins into their target membranes. Human cholangiocytes form an apical 'biliary bicarbonate umbrella' regarded as defense against harmful hydrophobic bile acid influx. The bicarbonate secretory machinery comprises the chloride/bicarbonate exchanger AE2 and the chloride channel ANO1. We aimed to investigate the expression and function of annexin A11 in human cholangiocytes and a potential role of IgG1/IgG4-mediated autoreactivity against annexin A11 in the pathogenesis of IRC.
methodsExpression of annexin A11 in human liver was studied by immunohistochemistry and immunofluorescence. In human control and ANXA11 knockdown H69 cholangiocytes, intracellular pH, AE2 and ANO1 surface expression, and bile acid influx were examined using ratio microspectrofluorometry, cell surface biotinylation, and 22,23-
resultsAnnexin A11 was strongly expressed in human cholangiocytes, but not hepatocytes. Knockdown of ANXA11 led to reduced plasma membrane expression of ANO1, but not AE2, alkalization of intracellular pH and uncontrolled bile acid influx. High intracellular calcium conditions led to annexin A11 membrane shift and colocalization with ANO1. Incubation with IRC patient serum inhibited annexin A11 membrane shift and reduced ANO1 surface expression.
conclusionCholangiocellular annexin A11 mediates apical membrane abundance of the chloride channel ANO1, thereby supporting biliary bicarbonate secretion. Insertion is inhibited by IRC patient serum containing anti-annexin A11 IgG1/IgG4-autoantibodies. Anti-annexin A11 autoantibodies may contribute to the pathogenesis of IRC by weakening the 'biliary bicarbonate umbrella'. LAY SUMMARY: We previously identified annexin A11 as a specific autoantigen in immunoglobulin G4-related cholangitis (IRC), a B-cell driven disease affecting the bile ducts. Human cholangiocytes are protected against harmful hydrophobic bile acid influx by a defense mechanism referred to as the 'biliary bicarbonate umbrella'. We found that annexin A11 is required for the formation of a robust bicarbonate umbrella. Binding of patient-derived annexin A11 autoantibodies inhibits annexin A11 function, possibly contributing to bile duct damage by weakening the biliary bicarbonate umbrella in patients with IRC.
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